Cough and rhinorrhea are generally present in patients throughout the first week of influenza infection, whereas upper respiratory symptoms are associated with the first several days of influenza infection and lower respiratory symptoms are associated with the end of the first week of infection. These are among study findings published in Influenza and Other Respiratory Viruses.
Although international public health organizations have attempted to define influenza in terms of specific viral symptoms, some research suggests this approach may be limited due to the dynamic changes in symptoms during the course of an influenza infection. Researchers therefore conducted an international, prospective cohort study to examine changes in influenza symptoms over time in adults with fever and other symptoms associated with the virus.
A total of 2471 patients (median age, 39 years; 46.6% male) were enrolled in the study during 5 consecutive influenza seasons, from 2015 to 2020. Study participants were recruited from the emergency departments of a surveillance network of 4 US hospitals and 3 hospitals in Taiwan from November 2015 to March 2020. Eligible participants were those younger than 18 years old who visited the emergency department and either: 1) had fever or other symptoms associated with influenza; 2) had no symptoms of respiratory infection; or 3) tested positive for influenza during the hospital visit.
Of the cohort, 994 patients (40.2%) tested positive for influenza virus infection, with 70% recruited in H1N1-dominant seasons. Cough was the most common symptom in patients who tested positive for influenza virus infection (sensitivity: 96.2%; 95% CI, 94%-97.6%), followed by fatigue (88.9%; 95% CI, 85.7%-91.4%), and body ache (84.9%; 95% CI, 81.3%-87.8%). Patients with influenza virus infection were more likely to have cough (odds ratio [OR], 12.96; 95% CI, 9.28-18.10), fatigue (OR, 2.86; 95% CI, 2.27-3.6), and rhinorrhea (OR, 2.81; 95% CI, 2.35-3.36), compared with those who tested negative for influenza virus infection.
The participants also were grouped into 4 quartiles based on their days of illness in the first week of symptom onset. A greater number of patients with influenza virus infection presented to the emergency department in the first half of the week after symptom onset (60.6% within 1 to 3 days). A majority of symptoms were predictive of influenza virus infection within the first 2 days of illness (OR, 1.55-10.28).
Of 19 symptoms observed, cough was the strongest predictor throughout the week (OR, 7.08-11.15), and rhinorrhea also was predictive throughout the week (OR, 1.72-2.51). General symptoms such as headache, chills, and fatigue as well as other upper respiratory symptoms such as sore throat and productive cough only were predictive of influenza virus infection in the first half of the week (1-3 days; OR, 1.55-3.25).
In the second half of the week, lower respiratory symptoms, including shortness of breath, wheezing, and chest pain, were predictive of influenza virus infection (4-7 days; OR, 2.52-1.52).
In a subgroup analysis, participants who were vaccinated for influenza were older and had more comorbidities than those who were unvaccinated. Comorbidities included diabetes, end-stage kidney disease, and asthma. In addition, lower respiratory symptoms were predictive of influenza breakthrough infection throughout the week (shortness of breath, OR, 2.06-2.95), and general symptoms such as headache and chills were not predictive of influenza virus infection in the influenza-vaccinated participants. Patients with influenza virus infection in the United States generally had a greater number of lower respiratory symptoms and fewer sore throat symptoms.
Among several limitations, the researchers modified the definition of influenza-like illness to include fever and at least 1 of the 3 respiratory symptoms. Also, the participants were interviewed only once during their visits to the emergency department, and symptoms were accumulated at enrollment instead of from a daily log. Furthermore, patients who enrolled in the first half of the week were more likely to have influenza vs those enrolled in the second half of the week, and the study was conducted at multiple sites in Taiwan and the United States.
“In conclusion, the time course is an essential factor to be considered when attempting to predict influenza virus infection by symptoms,” stated the study authors. “Understanding the time course of influenza symptoms would be helpful for clinicians to treat patients with influenza-like illnesses.”
Li J-H, Wu C-C, Tseng Y-J, et al. Applying symptom dynamics to accurately predict influenza virus infection: an international multicenter influenza-like illness surveillance study. Influenza Other Respir Viruses. Published online December 8, 2022. doi:10.1111/irv.13081